Little is known about long-term influence of childhood psychopharmacologic stimulant treatment. Among prospective, controlled follow-up studies that have assessed treated and untreated children with ADHD, one found that medication reduced the risk for substance use disorder (SUD), another found that childhood stimulant treatment increased the risk, and a third showed no significant difference in outcome. Reconciling these inconsistencies is difficult due to methodological differences and limitations across studies. Also, it is difficult to disentangle the effects of treatment from those of clinical status on the development of SUD since children with continued behavior problems are likely to be maintained on stimulants. Determining the effects of childhood pharmacotherapy on outcome has important implications since this knowledge would permit clinicians and parents to make informed judgments concerning the cost/benefit ratio of treatment in children. The main objective of this application is to determine whether stimulant treatment in childhood confers increased risk for SUD in later life. We have a unique opportunity to address this goal. We conducted a prospective, controlled follow-up study of children with reading disorder who were randomly assigned to methylphenidate or placebo between ages 7 and 12 yrs (mean, 10 yrs). Importantly, the children did not receive medication beyond their study treatment, and their exposure to stimulants is not complicated by aspects of clinical management. At l6 year follow-up (mean age, 26 yrs), 91% (n = 102) of the index subjects and 129 comparisons were systematically evaluated by trained clinicians who were blind to their childhood status. We previously reported that subjects with reading disorders who were unselected for treatment status were at significantly increased risk for SUD in adulthood. The main goal of this application is to examine whether there are differences between stimulant treated and untreated probands in the rate of SUD, and whether the rates of SUD in each of the proband groups differ from those in normal comparisons. We will also investigate other outcome measures and the interactional or additive effects of other childhood variables to assess the impact of childhood stimulant treatment on multiple domains of adjustment.